a study to assess safety and efficacy of avalglucosidase alfa administered every other week in pediatric patients with infantile-onset pompe disease previously treated with alglucosidase alfa

Conditions: Glycogen Storage Disease Type II-Pompe's Disease

Summary: this is a multi-stage, phase 2, open-label, multicenter, multinational, ascending dose cohort, repeated intravenous (iv) infusion study of avalglucosidase alfa in pediatric patients with infantile-onset pompe disease (iopd) who have been previously treated with alglucosidase alfa for a minimum of 6 months immediately prior to study entry and have demonstrated clinical decline or unsatisfactory clinical response.

the duration of the study for each participant will be up to 8 years and 9 months that will consist of a 14-day screening period, that may be extended to up to 4 weeks in pre-specified situations. this is followed by a 25-week treatment period and an up to a 430-week treatment extension period and a 4-week post-treatment observation period. cohort 1 and 2 (cohort 1: avalglucosidase alfa 20 milligrams per kilogram \[mg/kg\], cohort 2: avalglucosidase alfa 40 mg/kg) will be non-randomized and cohort 3 (cohort 3a: avalglucosidase alfa 40 mg/kg \[maximum tolerated dose\] and cohort 3b: alglucosidase alfa) will be randomized.

Eligibility criteria:
inclusion criteria: * the participants has confirmed acid alpha-glucosidase (gaa) enzyme deficiency from any tissue source. * the participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. if the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable. * the participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol. * the participants is less than 18 years old. * the participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/baseline. * the participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (lvmi) equivalent to mean age specific lvmi plus 2 standard deviations. * the participant has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry. * for participants in stage 1: the participant has documented evidence of clinical decline in at least 1 of the following parameters related to pompe disease and not related to intercurrent illness as assessed by the investigator: respiratory function, motor skills, and/or cardiac parameters. * for participants in stage 2: the participant has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to pompe disease and not related to intercurrent illness as assessed by the investigator: respiratory function, motor skills, and/or new onset of ptosis. exclusion criteria: participants are excluded from the study if any of the following criteria apply: * the participant has high antibody titer to alglucosidase alfa. * the participant has a high risk for a severe allergic reaction to neogaa (avalglucosidase alfa). * the participant requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study. * the participant has previously participated in any act14132 study cohort. * female participant of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to tested for pregnancy. the above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.